高毒力肺炎克雷伯菌两种金黄地鼠呼吸道感染模型比较研究  

Two golden hamster models of hypervirulent Klebsiella pneumoniae respiratory infection:a comparative study

作　　者：张之珺 张丽丽 吕蒙 周冬生 杨文慧 高波[2] ZHANG Zhijun;ZHANG Lili;LÜMeng;ZHOU Dongsheng;YANG Wenhui;GAO Bo(State Key Laboratory of Pathogen and Biosecurity,Institute of Microbiology and Epidemiology,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100071,China;Institute of Military Cognition and Brain Sciences,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China)

机构地区：[1]军事科学院军事医学研究院微生物流行病研究所,病原微生物生物安全国家重点实验室,北京100071 [2]军事科学院军事医学研究院军事认知与脑科学研究所,北京100850

出　　处：《军事医学》2024年第1期30-35,共6页Military Medical Sciences

基　　金：国家重点研发计划项目(2023YFC2605000);病原微生物生物安全国家重点实验室自主研究课题(SKLPBS2225)。

摘　　要：目的建立高毒力肺炎克雷伯菌经气溶胶肺递送和滴鼻感染金黄地鼠动物模型,并对比两种模型的构建效果。方法选取4~5周龄雄性金黄地鼠,经气溶胶肺递送和滴鼻两种途径攻毒高毒力肺炎克雷伯菌NTUHK2044,记录金黄地鼠攻毒后14 d的生存状况,计算两种途径的半数致死量、存活率,并对呼吸道沉积分布、肺部细菌载量及组织病理进行检测。结果气溶胶肺递送途径攻毒引起金黄地鼠半数死亡剂量(3×10^(4)CFU)低于滴鼻途径(7×10^(5)CFU)。4×10^(6)CFU高毒力肺炎克雷伯菌以气溶胶肺递送途径感染金黄地鼠后,96.46%沉积在肺部并成功定植,主要引起大叶性肺炎,4 d内动物全部死亡;而同等剂量菌液滴鼻后95.62%沉积在口鼻部,随后下移至气管定植,主要引起支气管肺炎,病变程度相对较轻,细菌更易被机体清除,14 d存活率为70%。结论细菌呼吸道感染造模效果受攻毒途径影响,高毒力肺炎克雷伯菌经气溶胶肺递送攻毒主要引起病变严重的大叶性肺炎,滴鼻则主要引起病变较轻的支气管肺炎。上述两种动物模型的成功建立可为肺炎克雷伯菌致病机制研究和药效评价提供关键支撑。Objective To establish two golden hamster models infected with hypervirulent Klebsiella pneumoniae via aerosolizedintratracheal(i.t.)andintranasal(i.n.)inoculation,andcomparetheirproperties.Methods Goldenhamsters of 4 to 5 weeks old were exposed to K.pneumoniae NTUH⁃K2044 via i.t.route and i.n.route respectively.The survival of these golden hamsters was observed and recorded within 14 days of infection before the 50%lethal dose(LD50),survival rate,bacterial respiratory deposition rate,lung bacterial load and histopathology of the infected golden hamsters in the two groups were detected.Results The LD50 of the i.t.route(3×10^(4)CFU)was lower than that of the i.n.route(7×10^(5)CFU)in golden hamsters.After 4×10^(6)CFU NTUH⁃K2044 infection,the golden hamsters in the i.t.group had 96.46%of the bacteria deposited and colonized in the lung,developed lobar pneumonia and died without exception within 4 days of infection,while those in the i.n.group had 95.62%of the bacteria deposited in the mouth and nose initially before the bacteria moved down to the trachea for colonization and were cleared out gradually.This group mainly acquired bronchopneumonia with relatively mild lung lesions,with a 14⁃day survival rate of 70%.Conclusion Inoculation routes can make a difference to the disease type of respiratory tract infections in animal models.The i.t.route mainly causes lobar pneumonia with severe lung lesions,while the i.n.route leads to bronchopneumonia with mild lung lesions.The two animal models established above may be utilized for pathogenesis investigation and treatment efficacy evaluation of Klebsiella pneumoniae.

关 键 词：高毒力肺炎克雷伯菌 气溶胶 金黄地鼠 动物模型 

分 类 号：R332[医药卫生—人体生理学]